Hypofractionated Radiotherapy Matches Standard Treatment in High-Risk Breast Cancer: Study
A Danish phase III trial has found that hypofractionated locoregional radiotherapy (40 Gy in 15 fractions over 3 weeks) was noninferior to standard radiotherapy (50 Gy in 25 fractions over 5 weeks) for high-risk breast cancer. Both regimens showed similar 3-year rates of arm lymphedema, with no significant differences in locoregional or distant recurrence, breast cancer mortality, or overall mortality, supporting the shorter treatment schedule as an effective alternative.
The study was published in the Journal of Clinical Oncology by Birgitte V. and colleagues. For the purpose of comparing morbidity of the upper extremity and oncologic outcomes after treatment according to standard and hypofractionated radiation regimens, the DBCG Skagen Trial 1 trial was launched from 2015 to 2021 across 17 institutions. High-risk patients with breast cancer who required full locoregional irradiation were randomized at a ratio of 1:1 to receive either standard normofractionation (50 Gy in 25 fractions) or experimental hypofractionation (40 Gy in 15 fractions).
The primary outcome of this trial was the 3-year cumulative incidence of arm lymphedema, and non-inferiority was pre-specified as the maximal excess incidence of 5 percentage points among patients in the 40 Gy group assuming a baseline incidence rate of 10% in the 50 Gy arm. Patient recruitment was continued until 3-year morbidity was available in at least 1,012 participants, whereas survival and recurrence rates were recorded for a median follow-up time of over five years.
Key findings:
- A total of 2,908 participants were involved in the intention-to-treat analysis (1,444 in the 50 Gy group [50%] and 1,464 in the 40 Gy group [50%]).
- The average age of the participants was 57 years (range between 23 and 86 years).
- After three years of treatment, the rate of lymphedema in the 50 Gy group was 9.4% compared to 8.0% in the 40 Gy group (odds ratio = 0.84; 95% CI = 0.62–1.14; P = 0.27).
- The locoregional recurrence was 0.96 (95% CI = 0.62–1.51) in the eight years of follow-up (average follow-up to study cancer outcome = 5.25).
- No differences were identified in the risk ratios of distant recurrence (HR = 1.10; 95% CI = 0.89–1.37), breast cancer mortality (HR = 1.25; 95% CI = 0.93–1.66), or overall mortality (HR = 1.08; 95% CI = 0.85–1.36).
To conclude, it can be stated that the treatment with 40Gy/15fx of BC did not cause higher levels of lymphedema than the one seen after 50Gy/25fx and there were no statistically significant distinctions between randomization arms regarding locoregional or distant recurrences, breast cancer mortality, and all-cause mortality. The outcomes of the DBCG Skagen Trial 1 provide clear evidence that 3-week 40 Gy/15 fraction hypofractionated regimens should be used for locoregional irradiation of breast cancer.
Reference:
Offersen, B. V., Alsner, J., Høgsbjerg, K., Nielsen, H. M., Maae, E., Nielsen, M. H., Mjaaland, I., Maraldo, M. V., Kirkove, C., Lörincz, T., Al-Rawi, S., Blix, E. S., Schreiber, A., Krause, M., Kasti, U.-M., Matthiessen, L. W., Kronborg, C., Tramm, T., Jensen, M.-B., & Overgaard, J. (2026). Hypo- Versus Standard Fractionated Locoregional Radiotherapy of Patients With High-Risk Breast Cancer in the Randomized Phase III Trial: The Danish Breast Cancer Group Skagen Trial 1. Journal of Clinical Oncology. https://doi.org/10.1200/jco-25-02705
